Molecular Biology Reports

, Volume 46, Issue 3, pp 3417–3426 | Cite as

Identification of eleven different mutations including six novel, in the arylsulfatase B gene in Iranian patients with mucopolysaccharidosis type VI

  • Rokhsareh Jafaryazdi
  • Sedigheh Shams
  • Anna Isaian
  • Aria Setoodeh
  • Shahram TeimourianEmail author
Original Article


Mucopolysaccharidosis VI is a rare autosomal recessive disorder caused by the deficiency of enzyme Arylsulfatase B. The enzyme deficiency leads to the accumulation of dermatan sulfate in connective tissue which causes manifestations related to MPS VI. Up to now, three different disease causing variants are reported in Iranian patients. In this study, we scanned ARSB gene of 13 Iranian patients from 12 families in whom all parents were consanguineous and from the same ethnicity except one family that were not consanguineous but co-ethnic. We found six not previously reported disease causing variants. We extracted DNA from peripheral blood samples of patients that were previously confirmed as MPS VI by clinical, biochemical and enzymatic assays including berry-spot test and fluorimetry, followed by PCR and direct sequencing. Computational approaches were used to analyze novel variants in terms of their impact on the protein structure. 11 disease causing variants and 15 polymorphisms were found. Six disease causing variants were novel and five were previously reported of which three were in Iranian population. Four of patients, who were unrelated, two by two had the same disease causing variant and polymorphisms, which indicates a possible founder effect. Our study also implicates genotype–phenotype correlation. Computational structural modeling indicated these disease causing variants might affect structural stability and function of the protein. Data of this study confirms the existence of mutational heterogeneity in the ARSB between Iranian patients. Disease causing variants with high frequency can be used in the prenatal diagnosis and genetic counseling. Also, the existence of the same variants and polymorphisms in some of the unrelated patients indicates a possible founder effect.


Arylsulfatase B MPS VI In silico Iran Sanger sequencing Variant 



The authors appreciate the patient family who kindly contributed to this study. The authors thank Ms. Neda Konkouri and Ms. Zhilla Poursheikhi who helped us in the blood sampling process. The authors declare there is no conflict of interest.


This study is funded by Iran University of medical sciences (IUMS), Iran. Grant Number 96-03-30-30735. This study is part of Miss. Jafaryazdi MSc thesis.

Compliance with ethical standards

Conflict of interest

The authors declare there is no conflict of interests.

Ethical approval

All of the ethical standards were approved by the responsible committee (Iran University of Medical Sciences, Faculty of Medicine).

Informed consent

All participants or their parents, whenever needed, signed informed consent forms.

Supplementary material

11033_2019_4804_MOESM1_ESM.docx (270 kb)
Supplementary material 1 (DOCX 269 kb)
11033_2019_4804_MOESM2_ESM.docx (1 mb)
Supplementary material 2 (DOCX 1068 kb)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Rokhsareh Jafaryazdi
    • 1
  • Sedigheh Shams
    • 2
    • 3
    • 4
  • Anna Isaian
    • 2
    • 3
  • Aria Setoodeh
    • 5
  • Shahram Teimourian
    • 1
    Email author
  1. 1.Department of Medical Genetics and Molecular BiologyIran University of Medical SciencesTehranIran
  2. 2.Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical SciencesTehranIran
  3. 3.Department of PathologyTehran University of Medical SciencesTehranIran
  4. 4.Pediatric Urology Research Center, Tehran University of Medical SciencesTehranIran
  5. 5.Division of Pediatrics Endocrinology, Children’s Medical CenterPediatrics Center of Excellence, Tehran University of Medical SciencesTehranIran

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